Brown and beige thermogenic adipocytes are specialized in energy consumption and linked to metabolic health. Canonically, thermogenic adipocytes are thought to be derived from mesenchymal PdgfRα+ adipocyte progenitor cells (APC) . We recently identified a novel population of cold-recruited APCs from the vascular smooth muscle lineage marked by the expression of the ion channel Trpv1 in mouse adipose tissue. To determine the function of the Trpv1+ APC-derived adipocytes, we impaired their adipogenic capacity by deletion of Pparγ in Trpv1-expressing cells in mice (Trpv1-Cre::Pparγ-flox) . Inhibition of de novo adipogenesis from Trpv1+ APCs resulted in modest changes in brown adipose tissue, but it caused a marked reduction in the expression of cold-induced browning genes, including UCP1, in white adipose tissue (WAT) , indicating impaired beige adipogenesis. Interestingly, Trpv1-Cre::Pparγ-flox mice did not show altered weight gain, glucose tolerance, or insulin sensitivity on either regular chow or high-fat diets. This discrepancy led us to search for potential compensatory mechanisms. We observed increased PdgfRα expression in WAT of Trpv1-Cre::Pparγ-flox animals, suggesting that impaired adipogenic capacity of the Trpv1+ APCs may trigger recruitment of the PdgfRα+ APCs. Additionally, while UCP1 expression was noticeably reduced in the beige adipocytes within WAT, the expression of transcripts involved in the UCP1-independent thermogenic pathways, including Ckmt1, Gatm, and Slc6a8, key components of the creatine futile cycle, was increased in the WAT of the Trpv1-Cre::Pparγ-flox mice upon cold exposure. Together, these data highlight a potential distinction between the thermogenic pathways mediated by adipocytes derived from the Trpv1+ versus those derived from the PdgfRα+ APCs. This functional difference of thermogenic adipocytes could be critical in designing strategies to target these cells as a therapeutic approach for metabolic diseases.
H.Camara: None. F.Shamsi: None. M.Lynes: None. Y.Tseng: Consultant; Cellarity.
National Institutes of Health (R01DK102898)